Evidence mapPaperPMID 40920270Full record

ArticleMetabolic brain disease2025

TLR-4/Notch1/NF-κB pathway modulation by dapagliflozin: a novel mechanism for neuroprotection in hepatic encephalopathy.

Hossam H Abouzaid, Muhammed F El-Yamany, Yasser O Mosaad, Mohamed M Sayed-Ahmed, Riham M Karkeet, Ayman E El-Sahar

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Article in Metabolic brain disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Hossam H AbouzaidDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Muhammed F El-YamanyDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Yasser O MosaadDepartment of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Future University, Cairo, Egypt.
Mohamed M Sayed-AhmedDepartment of Cancer Biology, Pharmacology and Experimental Oncology Unit, National Cancer Institute, Cairo University, Cairo, Egypt.
Riham M KarkeetDepartment of Cancer Biology, Pharmacology and Experimental Oncology Unit, National Cancer Institute, Cairo University, Cairo, Egypt. riham.karkeet@nci.cu.edu.eg.
Ayman E El-SaharDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute or chronic liver damage can result in Hepatic Encephalopathy (HE), a potentially fatal neuropsychiatric condition that leads to cerebral and neurological alterations. Dapagliflozin (DAPA), an orally active Sodium/Glucose cotransporter 2 inhibitor with long duration of action. The study aim was to evaluate the potential protective impact of DAPA against HE caused by Thioacetamide (TAA) in rats. HE was achieved via a single intraperitoneal TAA dosage of (300 mg/kg). DAPA was administered orally as (1 mg/kg) for 28 days. A total of forty rats were distributed randomly into 4 equal groups: Control (CTRL), Dapagliflozin (DAPA + CTRL), Thioacetamide (TAA), and Dapagliflozin plus Thioacetamide (DAPA + TAA). TAA induced cognitive impairment was alleviated by DAPA, as evidenced by reduction by 63% in escape latency of Morris water maze (MWM) test, elevation in fall off period of Rotarod test, and reduced serum ammonia, Liver enzymes, and restore normal serum albumin levels. DAPA improved the antioxidant capacity and activity of Glutathione by 87.53%; reduced apoptosis, liver necrosis, and astrocyte inflammation. Moreover, DAPA administration reduced gene expression of both Notch1 by 50% and TLR-4 by 55.65% suppressing release of inflammatory cytokines. In conclusion, DAPA possesses a neuroprotective effect, as confirmed by the enhancement of motor incoordination, cognitive deficits, and histopathological alterations. This neuroprotective impact can be justified by lowering hyperammonemia, improving liver functions, in addition to its antioxidant effect, and suppression of TLR-4/Notch1/NF-κB inflammatory pathway.

Indexed as

Benzhydryl CompoundsGlucosidesHepatic EncephalopathyNeuroprotective AgentsNF-kappa BReceptor, Notch1Toll-Like Receptor 4AnimalsMaleNeuroprotectionRatsRats, WistarSignal TransductionThioacetamideBenzhydryl CompoundsdapagliflozinGlucosidesNeuroprotective AgentsNF-kappa BNotch1 protein, ratReceptor, Notch1ThioacetamideTlr4 protein, ratToll-Like Receptor 4DapagliflozinHepatic encephalopathyNotch1ThioacetamideTLR-4

Identifiers

PMID40920270
PMCPMC12417255

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.